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  • Title: Studies on the mechanisms of altered exocrine acinar cell differentiation and ductal metaplasia following nitrosamine exposure using hamster pancreatic explant organ culture.
    Author: Resau JH, Cottrell JR, Hudson EA, Trump BF, Jones RT.
    Journal: Carcinogenesis; 1985 Jan; 6(1):29-35. PubMed ID: 3967337.
    Abstract:
    Syrian golden hamster pancreatic organ explants were treated with either methylnitrosourea (MNU) or N-methyl-N-nitroso-N'-nitroguanidine (MNNG). In control explants treated with only dimethylsulfoxide, there was evidence of autophagy and crinophagy in acinar cells. Carcinogen-exposed explants showed increased numbers of autophagic and crinophagic vacuoles. In long-term cultured explants there was an increase in the number of ducts over zero time control tissues. Eosinophilic cells similar to hepatocyte-like cells were seen in 90% of the carcinogen-treated explant experiments and in 45% of the controls. Nitrosamine exposure did not induce an increase in the overall amount of necrosis measured morphometrically. Nitrosamine exposure in vitro appears to lead to a sequence of events that follow carcinogen metabolism by the acinar cells. The changes that follow include altered cell morphology and toxic cell injury evidenced by autophagic and crinophagic processes, regeneration of ductal appearing cells, the appearance of hepatocyte-like cells and an overall increase in the amount of ductal metaplasia. Within some of these ductal foci, several ductules show atypical features.
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